# BIOMATHEMATICS OF CYCLIN DURING CELL SENESCENCE

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 1993 · $107,816

## Abstract

Cell populations are often heterogeneous with regard to the ability of
their members to respond to stimuli such as hormonal growth factors.  As
a result, they may achieve a graded response at the level of the whole
cell population, even though the response may be all-or-none at the level
of the individual cell.  the proposed research uses cultured human
diploid fibroblasts as an experimentally accessible model for analysis
of the epi-genetic mechanisms underlying heterogeneity of proliferative
responsiveness.  Because this heterogeneity changes throughout the life
of the fibroblast population, diploid fibroblasts are also a widely-used
model system for the study of cellular aging.

The cyclins are a recently-discovered class of proteins that control the
ability of cells to divide.  We found that the level of cyclin mRNA
decreases throughout the life of the fibroblast population.  The mRNA
could therefore be the physiological 'memory' that determines the number
of population doublings before the fibroblasts senesce.  If so,
heterogeneity of the cells' ability to divide should be accompanied by
heterogeneity in the cells' expression of cyclin-like genes.
Accordingly, the general objective of this project is to develop
biomathematical models that may be used to predict the relation between
heterogeneity of the cells' ability to divide (measured by time-lapse
video microscopy) and the expression of cyclin-like genes (measured by
quantitative nucleic acid hybridization).

Specifically, we propose to develop biomathematical models to:  (1)
analyze the hypothesis that in cell populations that are grown under
optimal growth conditions, heterogeneity of the cells' ability to
proliferate is due to random autocatalytic synthesis and degradation of
cyclin-like mRNA, as well as random partitioning of the mRNA during cell
division; (2) analyze the hypothesis that during quiescence, cells
maintain a 'memory' or cyclin mRNA levels during prior growth, unless the
quiescence is so deep that the population's lifespan is shortened; (3)
analyze the hypothesis that chemical agents such as retinoic acid and TPA
modulate the lifespan of fibroblast populations by affecting the cell-to-
cell heterogeneity of cyclin mRNA levels.

## Key facts

- **NIH application ID:** 3123108
- **Project number:** 1R01AG011124-01
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **SAM.gov UEI:** C1CPANL3EWK4
- **Principal Investigator:** DAVID R RIGNEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $107,816
- **Award type:** 1
- **Project period:** 1993-01-01 → 1996-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123108

## Citation

> US National Institutes of Health, RePORTER application 3123108, BIOMATHEMATICS OF CYCLIN DURING CELL SENESCENCE (1R01AG011124-01). Retrieved via MORVS 2026-10-27 from https://api.morvs.ai/grant/nih/3123108. Licensed CC0.

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